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    SPHK1 sphingosine kinase 1 [ Homo sapiens (human) ]

    Gene ID: 8877, updated on 6-Jun-2017
    Official Symbol
    SPHK1provided by HGNC
    Official Full Name
    sphingosine kinase 1provided by HGNC
    Primary source
    HGNC:HGNC:11240
    See related
    Ensembl:ENSG00000176170 MIM:603730; Vega:OTTHUMG00000180177
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SPHK
    Summary
    The protein encoded by this gene catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a lipid mediator with both intra- and extracellular functions. Intracellularly, S1P regulates proliferation and survival, and extracellularly, it is a ligand for cell surface G protein-coupled receptors. This protein, and its product S1P, play a key role in TNF-alpha signaling and the NF-kappa-B activation pathway important in inflammatory, antiapoptotic, and immune processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
    Orthologs
    Location:
    17q25.1
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 17 NC_000017.11 (76382977..76387860)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (74372742..74383941)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene phosphoribosyl pyrophosphate synthetase associated protein 1 Neighboring gene RNA, U6 small nuclear 24, pseudogene Neighboring gene high mobility group nucleosomal binding domain 2 pseudogene 43 Neighboring gene ubiquitin conjugating enzyme E2 O Neighboring gene ribosomal protein L7 pseudogene 49 Neighboring gene aralkylamine N-acetyltransferase

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of sphingosine kinase 1 (SPHK1) in human B cells PubMed

    Go to the HIV-1, Human Interaction Database

    • Apelin signaling pathway, organism-specific biosystem (from KEGG)
      Apelin signaling pathway, organism-specific biosystemApelin is an endogenous peptide capable of binding the apelin receptor (APJ), which was originally described as an orphan G-protein-coupled receptor. Apelin and APJ are widely expressed in various ti...
    • Association of TriC/CCT with target proteins during biosynthesis, organism-specific biosystem (from REACTOME)
      Association of TriC/CCT with target proteins during biosynthesis, organism-specific biosystemTRiC has broad recognition specificities, but in the cell it interacts with only a defined set of substrates (Yam et al. 2008). Many of its substrates that are targeted during biosynthesis are conse...
    • Calcium signaling pathway, organism-specific biosystem (from KEGG)
      Calcium signaling pathway, organism-specific biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
    • Calcium signaling pathway, conserved biosystem (from KEGG)
      Calcium signaling pathway, conserved biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
    • Chaperonin-mediated protein folding, organism-specific biosystem (from REACTOME)
      Chaperonin-mediated protein folding, organism-specific biosystemThe eukaryotic chaperonin TCP-1 ring complex (TRiC/ CCT) plays an essential role in the folding of a subset of proteins prominent among which are the actins and tubulins (reviewed in Altschuler and...
    • Fc gamma R-mediated phagocytosis, organism-specific biosystem (from KEGG)
      Fc gamma R-mediated phagocytosis, organism-specific biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
    • Fc gamma R-mediated phagocytosis, conserved biosystem (from KEGG)
      Fc gamma R-mediated phagocytosis, conserved biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
    • Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem (from Pathway Interaction Database)
      Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem
      Fc-epsilon receptor I signaling in mast cells
    • Metabolic pathways, organism-specific biosystem (from KEGG)
      Metabolic pathways, organism-specific biosystem
      Metabolic pathways
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
      Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • PDGFR-beta signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      PDGFR-beta signaling pathway, organism-specific biosystem
      PDGFR-beta signaling pathway
    • Phospholipase D signaling pathway, organism-specific biosystem (from KEGG)
      Phospholipase D signaling pathway, organism-specific biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
    • Phospholipase D signaling pathway, conserved biosystem (from KEGG)
      Phospholipase D signaling pathway, conserved biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
    • Protein folding, organism-specific biosystem (from REACTOME)
      Protein folding, organism-specific biosystemDue to the crowded envirnoment within the cell, many proteins must interact with molecular chaperones to attain their native conformation (reviewed in Young et al., 2004). Chaperones recognize and...
    • S1P1 pathway, organism-specific biosystem (from Pathway Interaction Database)
      S1P1 pathway, organism-specific biosystem
      S1P1 pathway
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signal Transduction of S1P Receptor, organism-specific biosystem (from WikiPathways)
      Signal Transduction of S1P Receptor, organism-specific biosystemMetabolism of sphingomyelin by the sphingomyelinase, ceramidase (Cer'ase) and the sphingosine kinase (SK) enzymes results in formation of S1P and receptor activation. Autocrine and paracrine modes of...
    • Signaling by VEGF, organism-specific biosystem (from REACTOME)
      Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
    • Sphingolipid Metabolism, organism-specific biosystem (from WikiPathways)
      Sphingolipid Metabolism, organism-specific biosystemThe sphingolipid metabolites and genes (with the gene abbreviations shown in boxes, or enzyme names where gene names are ambiguous) are given for the condensation of serine and palmitoyl-CoA to form ...
    • Sphingolipid de novo biosynthesis, organism-specific biosystem (from REACTOME)
      Sphingolipid de novo biosynthesis, organism-specific biosystemThe main steps involved in de novo sphingolipid synthesis are annotated here (Merrill 2002, Gault et al. 2010).
    • Sphingolipid metabolism, organism-specific biosystem (from KEGG)
      Sphingolipid metabolism, organism-specific biosystem
      Sphingolipid metabolism
    • Sphingolipid metabolism, organism-specific biosystem (from REACTOME)
      Sphingolipid metabolism, organism-specific biosystemSphingolipids are derivatives of long chain sphingoid bases such as sphingosine (trans-1,3-dihydroxy 2-amino-4-octadecene), an 18-carbon unsaturated amino alcohol which is the most abundant sphingoid...
    • Sphingolipid metabolism, conserved biosystem (from KEGG)
      Sphingolipid metabolism, conserved biosystem
      Sphingolipid metabolism
    • Sphingolipid signaling pathway, organism-specific biosystem (from KEGG)
      Sphingolipid signaling pathway, organism-specific biosystemSphingomyelin (SM) and its metabolic products are now known to have second messenger functions in a variety of cellular signaling pathways. Particularly, the sphingolipid metabolites, ceramide (Cer) ...
    • Sphingolipid signaling pathway, conserved biosystem (from KEGG)
      Sphingolipid signaling pathway, conserved biosystemSphingomyelin (SM) and its metabolic products are now known to have second messenger functions in a variety of cellular signaling pathways. Particularly, the sphingolipid metabolites, ceramide (Cer) ...
    • Sphingosine 1-phosphate (S1P) pathway, organism-specific biosystem (from Pathway Interaction Database)
      Sphingosine 1-phosphate (S1P) pathway, organism-specific biosystem
      Sphingosine 1-phosphate (S1P) pathway
    • Sphingosine degradation, organism-specific biosystem (from KEGG)
      Sphingosine degradation, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
    • Sphingosine degradation, conserved biosystem (from KEGG)
      Sphingosine degradation, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
    • Tuberculosis, organism-specific biosystem (from KEGG)
      Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
    • Tuberculosis, conserved biosystem (from KEGG)
      Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
    • VEGF signaling pathway, organism-specific biosystem (from KEGG)
      VEGF signaling pathway, organism-specific biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • VEGF signaling pathway, conserved biosystem (from KEGG)
      VEGF signaling pathway, conserved biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • VEGFA-VEGFR2 Pathway, organism-specific biosystem (from REACTOME)
      VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...
    • VEGFR2 mediated cell proliferation, organism-specific biosystem (from REACTOME)
      VEGFR2 mediated cell proliferation, organism-specific biosystemVEGFR2 stimulates ERK not via GRB2-SOS-RAS, but via pY1175-dependent phosphorylation of PLC gamma and subsequent activation of PKCs. PKC plays an important mediatory role in the proliferative Ras/Raf...
    • sphingosine and sphingosine-1-phosphate metabolism, organism-specific biosystem (from BIOCYC)
      sphingosine and sphingosine-1-phosphate metabolism, organism-specific biosystemIn this pathway, ceramide, the breakdown product of sphingomyelin, is metabolized by ceramidase to generate : SPHINGOSINE, which has been shown to be produced during the early stages of apoptosis; : ...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    D-erythro-sphingosine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    D-erythro-sphingosine kinase activity TAS
    Traceable Author Statement
    more info
     
    DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    NAD+ kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    calmodulin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    magnesium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein phosphatase 2A binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    sphinganine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    sphinganine kinase activity TAS
    Traceable Author Statement
    more info
     
    sphingosine-1-phosphate receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    blood vessel development IEA
    Inferred from Electronic Annotation
    more info
     
    brain development IEA
    Inferred from Electronic Annotation
    more info
     
    calcium-mediated signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    inflammatory response IEA
    Inferred from Electronic Annotation
    more info
     
    intracellular signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    lipid phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of NF-kappaB import into nucleus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of NF-kappaB transcription factor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of angiogenesis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of cell growth IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of cell migration IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of fibroblast proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of mitotic cell cycle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of peptidyl-threonine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of smooth muscle contraction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein folding TAS
    Traceable Author Statement
    more info
     
    regulation of interleukin-1 beta production IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of tumor necrosis factor-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    sphingoid catabolic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    sphingolipid biosynthetic process TAS
    Traceable Author Statement
    more info
     
    sphingosine biosynthetic process IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    sphingosine biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    sphingosine metabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    sphingosine-1-phosphate signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol IDA
    Inferred from Direct Assay
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
    PubMed 
    nucleus IEA
    Inferred from Electronic Annotation
    more info
     
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    sphingosine kinase 1
    Names
    SK 1
    SPK 1
    NP_001136073.1
    NP_001136074.1
    NP_068807.2
    NP_892010.2
    XP_005257823.1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001142601.1NP_001136073.1  sphingosine kinase 1 isoform 3

      See identical proteins and their annotated locations for NP_001136073.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) contains an alternate in-frame segment in the 5' coding region and uses a downstream start codon, compared to variant 2. Isoform 3 has a shorter N-terminus, compared to isoform 2. Variants 3 and 4 encode the same isoform, isoform 3.
      Source sequence(s)
      AK022402, BC009419, BC030553, DC384776
      Consensus CDS
      CCDS45785.1
      UniProtKB/Swiss-Prot
      Q9NYA1
      UniProtKB/TrEMBL
      Q53ZR5
      Related
      ENSP00000465726.1, OTTHUMP00000263536, ENST00000592299.5, OTTHUMT00000450117
      Conserved Domains (2) summary
      PLN02958
      Location:11345
      PLN02958; diacylglycerol kinase/D-erythro-sphingosine kinase
      pfam00781
      Location:16121
      DAGK_cat; Diacylglycerol kinase catalytic domain
    2. NM_001142602.1NP_001136074.1  sphingosine kinase 1 isoform 3

      See identical proteins and their annotated locations for NP_001136074.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) contains an alternate in-frame segment in the 5' coding region and uses a downstream start codon, compared to variant 2. Isoform 3 has a shorter N-terminus, compared to isoform 2. Variants 3 and 4 encode the same isoform, isoform 3.
      Source sequence(s)
      BC009419, BC030553, BP304783, DC384776
      Consensus CDS
      CCDS45785.1
      UniProtKB/Swiss-Prot
      Q9NYA1
      UniProtKB/TrEMBL
      Q53ZR5
      Related
      ENSP00000376285.2, OTTHUMP00000263539, ENST00000392496.3, OTTHUMT00000450121
      Conserved Domains (2) summary
      PLN02958
      Location:11345
      PLN02958; diacylglycerol kinase/D-erythro-sphingosine kinase
      pfam00781
      Location:16121
      DAGK_cat; Diacylglycerol kinase catalytic domain
    3. NM_021972.3NP_068807.2  sphingosine kinase 1 isoform 1

      See identical proteins and their annotated locations for NP_068807.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) has multiple differences in the coding region, compared to variant 2. The resulting protein (isoform 1) has a shorter N-terminus and contains an additional in-frame portion of the 5' coding region, compared to isoform 2.
      Source sequence(s)
      AK022402, BC009419, BC030553, DC384776
      Consensus CDS
      CCDS59297.1
      UniProtKB/Swiss-Prot
      Q9NYA1
      Related
      ENSP00000468547.1, OTTHUMP00000263537, ENST00000590959.5, OTTHUMT00000450118
      Conserved Domains (2) summary
      PLN02958
      Location:25359
      PLN02958; diacylglycerol kinase/D-erythro-sphingosine kinase
      pfam00781
      Location:30135
      DAGK_cat; Diacylglycerol kinase catalytic domain
    4. NM_182965.2NP_892010.2  sphingosine kinase 1 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2).
      Source sequence(s)
      AK022402, BC009419, BC030553, DC384776
      Consensus CDS
      CCDS11744.1
      UniProtKB/Swiss-Prot
      Q9NYA1
      Related
      ENSP00000313681.3, OTTHUMP00000263538, ENST00000323374.8, OTTHUMT00000450120
      Conserved Domains (2) summary
      PLN02958
      Location:97431
      PLN02958; diacylglycerol kinase/D-erythro-sphingosine kinase
      pfam00781
      Location:102207
      DAGK_cat; Diacylglycerol kinase catalytic domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p7 Primary Assembly

      Range
      76382977..76387860
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005257766.2XP_005257823.1  sphingosine kinase 1 isoform X1

      See identical proteins and their annotated locations for XP_005257823.1

      UniProtKB/Swiss-Prot
      Q9NYA1
      UniProtKB/TrEMBL
      Q53ZR5
      Conserved Domains (2) summary
      PLN02958
      Location:11345
      PLN02958; diacylglycerol kinase/D-erythro-sphingosine kinase
      pfam00781
      Location:16121
      DAGK_cat; Diacylglycerol kinase catalytic domain

    Alternate CHM1_1.1

    Genomic

    1. NC_018928.2 Alternate CHM1_1.1

      Range
      74445769..74449020
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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